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Information on EC 2.7.7.3 - pantetheine-phosphate adenylyltransferase and Organism(s) Staphylococcus aureus and UniProt Accession P63819
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2.7.7.3 pantetheine-phosphate adenylyltransferaseIUBMB Comments
The enzyme from several bacteria (e.g. Escherichia coli, Bacillus subtilis and Haemophilus influenzae) has been shown to be bifunctional and also to possess the activity of EC 2.3.1.157, glucosamine-1-phosphate N-acetyltransferase.
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Word Map
- 2.7.7.3
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ppats
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penultimate
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dpcoa
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pantothen
- pyrophosphate
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hexameric
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3\'-dephospho-coa
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nucleotidyltransferase
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dephosphocoenzyme
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phosphopantothenoylcysteine
- medicine
- drug development
The taxonomic range for the selected organisms is: Staphylococcus aureus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
phosphopantetheine adenylyltransferase, 4'-phosphopantetheine adenylyltransferase, pantetheine phosphate adenylyltransferase, dephospho-coa pyrophosphorylase, enterococcus faecalis ppat, pantetheine-phosphate adenylyltransferase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
3'-dephospho-CoA pyrophosphorylase
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-
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dephospho-CoA pyrophosphorylase
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-
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dephospho-coenzyme A pyrophosphorylase
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pantetheine phosphate adenylyltransferase
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PPAT
PPAT
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
nucleotidyl group transfer
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PATHWAY SOURCE
PATHWAYS
BRENDA
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-, -, -
SYSTEMATIC NAME
IUBMB Comments
ATP:pantetheine-4'-phosphate adenylyltransferase
The enzyme from several bacteria (e.g. Escherichia coli, Bacillus subtilis and Haemophilus influenzae) has been shown to be bifunctional and also to possess the activity of EC 2.3.1.157, glucosamine-1-phosphate N-acetyltransferase.
CAS REGISTRY NUMBER
COMMENTARY
9026-99-7
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + 4'-phosphopantetheine
diphosphate + 3'-dephospho-CoA
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-
-
r
ATP + pantetheine 4'-phosphate
diphosphate + 3'-dephospho-CoA
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-
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r
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + pantetheine 4'-phosphate
diphosphate + 3'-dephospho-CoA
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-
-
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r
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(1S,2S)-N-(3,4-dichlorobenzyl)-2-(4,6-dimethoxypyrimidin-2-yl)cyclohexanecarboxamide
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(1S,2S)-N-(3-chlorobenzyl)-2-(4,6-dimethoxypyrimidin-2-yl)cyclohexanecarboxamide
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2'-[(1S,2S)-2-[(3,4-dichlorobenzyl)carbamoyl]cyclohexyl]-6'-ethyl-4-hydroxy-6-oxo-1,6-dihydro-2,4'-bipyrimidine-5-carboxamide
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2-[(2-[(1S,2S)-2-[(3,4-dichlorobenzyl)carbamoyl]cyclohexyl]-6-ethylpyrimidin-4-yl)sulfanyl]-1H-imidazole-5-carboxylic acid
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3-[3-(2-[(1S,2S)-2-[(3,4-dichlorobenzyl)carbamoyl]cyclohexyl]-6-ethylpyrimidin-4-yl)-1,2,4-oxadiazol-5-yl]propanoic acid
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additional information
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compound library screening, mode-of-inhibition studies with Staphylococcus aureus PPAT demonstrate representatives of this series to be reversible inhibitors competitive versus phosphopantetheine and uncompetitive versus ATP, binding to the enzyme-ATP complex, overview. The potency of the series is optimized using structure-based design, resulting in inhibition of cell growth of Gram-positive species. Levels of inhibitory activity of compounds against Staphylococcus aureus PPAT are measured in the forward direction, MIC values, mechanism of inhibition, overview
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00033
(1S,2S)-N-(3,4-dichlorobenzyl)-2-(4,6-dimethoxypyrimidin-2-yl)cyclohexanecarboxamide
Staphylococcus aureus
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pH 7.0, 22°C, recombinant enzyme
0.0073
(1S,2S)-N-(3-chlorobenzyl)-2-(4,6-dimethoxypyrimidin-2-yl)cyclohexanecarboxamide
Staphylococcus aureus
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pH 7.0, 22°C, recombinant enzyme
0.00000087
2'-[(1S,2S)-2-[(3,4-dichlorobenzyl)carbamoyl]cyclohexyl]-6'-ethyl-4-hydroxy-6-oxo-1,6-dihydro-2,4'-bipyrimidine-5-carboxamide
Staphylococcus aureus
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pH 7.0, 22°C, recombinant enzyme
0.00049
2-[(2-[(1S,2S)-2-[(3,4-dichlorobenzyl)carbamoyl]cyclohexyl]-6-ethylpyrimidin-4-yl)sulfanyl]-1H-imidazole-5-carboxylic acid
Staphylococcus aureus
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pH 7.0, 22°C, recombinant enzyme
0.00000041
3-[3-(2-[(1S,2S)-2-[(3,4-dichlorobenzyl)carbamoyl]cyclohexyl]-6-ethylpyrimidin-4-yl)-1,2,4-oxadiazol-5-yl]propanoic acid
Staphylococcus aureus
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pH 7.0, 22°C, recombinant enzyme
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
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enzyme inhibition causes growth suppression of the bacteria, e.g. of Staphylococcus aureus strain ARC516
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
enzyme from Staphylococcus aureus subsp. aureus MW2 in complex with inhibitors, vapour diffusion method, mixing of 0.0025 ml of protein solution with 0.0025 ml of reservoir solution containing 14% to 19% PEG 3350, 200 mM ammonium sulfate, and 0.1 M propionic acid cacodylate Bis-Tris propane buffer, pH 7.5, 20°C, 5-7 days, X-ray diffraction structure determination and analysis at 1.72-2.38 A resolution, molecular replacement and modelling of inhibitor binding
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
N106H
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the enzyme mutant is less sensitive to inhibition by compound D compared to the wild-type enzyme
N106Y
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the enzyme mutant is less sensitive to inhibition by compound D compared to the wild-type enzyme
V136F
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the enzyme mutant is less sensitive to inhibition by compound D compared to the wild-type enzyme
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Ni-nitrilotriacetic acid-agarose affinity chromatography, gel filtration
recombinant wild-type and mutant PPAT enzymes from Escherichia coli strain BL21(DE3) to over 90% purity
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene coaD, recombinant overexpression of wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Lee, H.H.; Yoon, H.J.; Kang, J.Y.; Park, J.H.; Kim, d.o..J.; Choi, K.H.; Lee, S.K.; Song, J.; Kim, H.J.; Suh, S.W.
The structure of Staphylococcus aureusphosphopantetheine adenylyltransferase in complex with 3-phosphoadenosine 5-phosphosulfate reveals a new ligand-binding mode
Acta Crystallogr. Sect. F
65
987-991
2009
Staphylococcus aureus (P63819), Staphylococcus aureus
de Jonge, B.L.; Walkup, G.K.; Lahiri, S.D.; Huynh, H.; Neckermann, G.; Utley, L.; Nash, T.J.; Brock, J.; San Martin, M.; Kutschke, A.; Johnstone, M.; Laganas, V.; Hajec, L.; Gu, R.F.; Ni, H.; Chen, B.; Hutchings, K.; Holt, E.; McKinney, D.; Gao, N.; Livchak, S.; Thresher, J.
Discovery of inhibitors of 4-phosphopantetheine adenylyltransferase (PPAT) to validate PPAT as a target for antibacterial therapy
Antimicrob. Agents Chemother.
57
6005-6015
2013
Candida albicans (B9WCR8), Enterococcus faecium, Enterococcus faecium ARC521, Escherichia coli (P0A6I6), Haemophilus influenzae (P44805), Haemophilus influenzae KW20 (P44805), Homo sapiens (Q06203), Staphylococcus aureus, Staphylococcus aureus RN4220, Streptococcus mutans (Q8DVH2), Streptococcus mutans UA159 (Q8DVH2), Streptococcus pneumoniae (Q8DNE6), Streptococcus pyogenes, Streptococcus pyogenes ARC838
EXTERNAL LINKS (specific for EC-Number 2.7.7.3)
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Release 2023.1 (January 2023)
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